Pregabalin is a pharmacologically active S-isomer of 3-aminomethyl-5-methylhexanoic acid. It is a GABA (gamma-aminobutyric acid) receptor antagonist developed by Pfizer, USA, and has a dose-dependent protective effect on epileptic seizure. Specifically, pregabalin is an analog of the neurotransmitter GABA, which exerts anti-epileptic effect by inhibiting the a2-subunit of the CNS voltage-dependent calcium channel, and has good lipid solubility to pass through the blood-brain barrier, showing better anti-epilepsy treatment effect in clinical trials.
Pregabalin first came into the market of UK in 2004. It was clinically used to treat neuropathic pain caused by diabetes, post-herpetic neuralgia, and adjuvant treatment of localized incomplete seizures in adult patients. It is the first drug approved by the FDA for the treatment of more than 2 types of neuropathic pain. The drug is administered less frequently and thus with less adverse reactions. In March 2006, indications were added for treating generalized anxiety disorder and social anxiety disorder. In June 2007, pregabalin was approved by the FDA as the first drug to treat fibromyalgia syndrome. In 2009, it was approved additionally for the treatment of spinal cord injury, trauma, multiple sclerosis, diabetic neuropathic pain and herpes zoster neuropathic pain.
Pregabalin is considered to be the most promising drug in epilepsy treatment because of its good anti-anxiety effect, good therapeutic effect on neuralgia and epilepsy, and convenient administration. 3-Isobutylglutaric acid monoamide is a very important intermediate in the chemical synthesis process of pregabalin.

The preparation of the pregabalin intermediate (3-isobutylglutaric acid monoamide) from 3-isobutylglutaric acid reported in the literature is basically carried out according to the two synthetic routes in the above reaction scheme 1. Wherein, in the first route (i.e., the route of Compound 1-Compound 2-Compound 4), when preparing compound 2, a high-temperature solvent-free reaction is employed, and then ring-opening reaction is performed on compound 2 to obtain 3-isobutylglutaric acid monoamide. The disadvantage of the process is that in the solvent-free reaction, the viscosity of the reaction system is so large that the stirring resistance is large, and the safety hazard is easy to occur; the process belongs to the solid-liquid reaction, and the urea as one of the reactants in the reaction process is easily crystallized on the reactor wall, which easily causes clogging of the distillation outlet and the exhaust gas line, thereby increasing the difficulty of cleaning, and also resulting in low urea utilization rate, incomplete reaction, low yield, and total yield of the two-step reaction is only about 60%-70%.